Ning J, Wu T-H, Tian Y, Wang C-Y, Tian G, Zhang B-J, Liu K-X, Ma X-C
School of Pharmacy, Dalian Medical University, Dalian, China.
Xenobiotica. 2010 Jan;40(1):48-54. doi: 10.3109/00498250903331049.
Cinobufagin (1) is a major bufadienolide in ChanSu (a traditional Chinese medicine) with a wide range of pharmacological activities. In this paper, the in vivo metabolites of 1 in rats were studied. Nine metabolites were isolated from the bile of rats, and their structures were identified as: desacetylcinobufagin (2), 3-ketodesacetylcinobufagin (3), 3-epi-desacetylcinobufagin (4); 5beta-hydroxy-3-epi-desacetylcinobufagin (5), 1alpha-hydroxy-3-epi-desacetylcinobufagin (6), 12beta-hydroxy-3-epi-desacetylcinobufagin (7), 1beta-hydroxy-3-epi-desacetylcinobufagin (8), 1alpha,5alpha-dihydroxy-3-epi-desacetylcino-bufagin (9), and 2alpha, 5beta-dihydroxy-3-epi-desacetylcinobufagin (10), respectively, on the basis of widely spectroscopic studies including two-dimensional-nuclear magnetic resonance (NMR). Among them, metabolites 6-10 are new compounds. The results show that hydroxylation is the main reaction involved in metabolism of 1, and the preferred hydroxylation sites were C-1 and C-5.
华蟾酥毒基（1）是蟾酥（一种传统中药）中的主要蟾蜍二烯羟酸内酯，具有广泛的药理活性。本文对1在大鼠体内的代谢产物进行了研究。从大鼠胆汁中分离出9种代谢产物，通过包括二维核磁共振（NMR）在内的广泛光谱研究确定了它们的结构，分别为：去乙酰华蟾酥毒基（2）、3-酮去乙酰华蟾酥毒基（3）、3-表去乙酰华蟾酥毒基（4）；5β-羟基-3-表去乙酰华蟾酥毒基（5）、1α-羟基-3-表去乙酰华蟾酥毒基（6）、12β-羟基-3-表去乙酰华蟾酥毒基（7）、1β-羟基-3-表去乙酰华蟾酥毒基（8）、1α,5α-二羟基-3-表去乙酰华蟾酥毒基（9）和2α,5β-二羟基-3-表去乙酰华蟾酥毒基（10）。其中，代谢产物6 - 10为新化合物。结果表明，羟基化是1代谢的主要反应，且优先羟基化位点为C-1和C-5。
